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Hypertensive, obese with CHD
44 years old

CASE PRESENTATION

  • The patient is now 44-years-old and weighs 119 kg
    He visited the clinic with a BP of 180/130 mm Hg
    He is complaining of gastric pain

    The ECG showed
    atrial fibrillation
    mean heart rate was 142 bpm
    frequent ventricular extra systoles
    Depressed ST segment in inferior leads

    He is unable to perform a treadmill test
    You realize a stress echo showing inferior hypokinesia
    An angiogram confirms stenosis of the second segment of the right CA, stented,
    Return in sinus rhythm

MEDICAL HISTORY

QUESTIONS

+ Do you think this is a case of hypertension-mediated organ damage.
  • YES
  • NO
SHOW ANSWER
YES Clinical evaluation and HMOD assessment - 1
Clinical evaluation and HMOD assessment - 2
+ How would you classify HTN according to blood pressure levels, presence of cardiovascular risk factors, HMOD, or comorbidities?
SHOW ANSWER
HTN Grade 3 with high to very high risk

Classification of hypertension stages according to BP levels, presence of CV risk factors, HMOD, or comorbidities
+ How should the case of HTN /atrial fibrillation/ CAD be treated?
  • ACEi or ARB + CCB or diuretic
  • ACEi or ARB + beta-blocker or CCB or CCB + diuretic or beta-blocker or beta-blocker + diuretic
  • ACEi or ARB + CCB or ACEi or ARB + diuretic (or loop diuretic)
  • ACEi or ARB + beta-blocker or non-DHP CCB, or beta blocker + CCB
Williams B et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. European Heart Journal. 2018. 39(33); 3021–3104
SHOW ANSWER
ACEi or ARB + beta-blocker or non-DHP CCB, or beta blocker + CCB

Drug-treatment strategy for hypertension and CAD

Beta-blocker in patients with CHD

Beta-blocker in patients with CHD - 2

Sympathetic overdrive increases the risk of cardiovascular and all-cause mortality in patients with CHD

Elevated heart rate is associated with acute ischemic events in patients with CHD

Bisoprolol was associated with a reduction in heart rate and frequency/duration/intensity of ischemic episodes in patients with stable angina

Bisoprolol reduced exercise-induced ischemic ST-segment depression in patients with stable CHD

Bisoprolol increased exercise tolerance and reduced ST-segment depression during exercise in patients with stable effort angina

Bisoprolol reduced ischemic episodes in patients with stable angina - 1

Bisoprolol reduced ischemic episodes in patients with stable angina - 2

Bisoprolol reduced ischemic episodes in patients with stable angina - 3

Bisoprolol reduced ischemic episodes in patients with stable angina - 4

Beta blockers for patients with obesity, hypertension, atrial fibrillation and CAD

Drug-treatment strategy for hypertension and AF
+ Do you think Bisoprolol can be the choice of drug to treat a similar case?
  • YES
  • NO
SHOW ANSWER
YES

EVIDENCE

Beta-blockers should be considered first line therapy to control the ventricular rate in patients with atrial fibrillation
They may also help to stabilize rhythm in patients with paroxysmal atrial fibrillation
They are preferred to Digoxin which is ineffective at limiting rate during exercise / sympathetic drive
Bisoprolol is the preferred oral therapy in patients with continuous atrial fibrillation
It is cardio-selective and offers good control of the ventricular rate
Starting dose is 2.5mg (1.25 mg in the elderly)
Bisoprolol exhibits a dose-responsive HR reduction when administered at sequential doses of 2.5 mg/day and 5 mg/day

Atrial Fibrillation. NHS Tayside. Available at https://www.nhstaysideadtc.scot.nhs.uk/TAPG%20html/pdf%20docs/Section%202artfib.pdf.

Bisoprolol in heart rate reduction and in atrial fibrillation
Various β-blockers are used to control HR in AF; however, there have been few quantitative assessments of HR and blood pressure reductions with β-blocker monotherapy

A study by Yamashita T et al studied the effect of bisoprolol (2.5 mg/day) for 2 weeks in 78 patients with chronic (persistent or permanent) AF

48 patients judged to require a dose increase were either continued on 2.5 mg/day (24 patients) or administered a higher dose (5 mg/day; 24 patients) in a double-blind fashion for two further weeks

Change in mean HR as determined by Holter electrocardiogram was the primary endpoint

After 2 weeks of bisoprolol 2.5 mg/day, mean HR was significantly lower than that before treatment (12.2 ± 9.1 beats/min, p < 0.001)

Mean HRs in the 5-mg and 2.5-mg continuation groups were also significantly decreased compared with those before treatment (17.3 ± 12.9 and 11.4 ± 7.4 beats/min, respectively, both p < 0.001), with a significant between-group difference (p = 0.033)

The HR reduction was greater during the day than at night

Although a greater reduction in systolic blood pressure was seen in the 5-mg group than in the 2.5-mg continuation group, the difference between groups was not significant

There were no serious adverse events

Yamashita T, Inoue H. Heart rate-reducing effects of bisoprolol in Japanese patients with chronic atrial fibrillation: Results of the MAIN-AF study. J Cardiol. 2013;62(1):50-57. doi:10.1016/j.jjcc.2013.02.010

WRAP UP

Objective:
The therapeutic approach should consider total CV risk in addition to BP levels in order to maximize cost-effectiveness of the management of hypertension.1

Efficacy
Greater SBP & DBP reduction vs. atenolol1, as well as other antihypertensive agents such as losartan, amlodipine and hydrochlorothiazide2 Better heart rate reduction vs. metoprolol,3 carvedilol and nebivolol4

β1-Selectivity
Bisoprolol is a third generation beta blocker with a remarkably high beta1-selectivity7

Safety profile
Minimal effects on blood glucose*, and lipids8-10, as well as lung function**8,11, peripheral circulation12-15, and male sexual function16
Consistent pharmacokinetic profile with a balanced renal clearance and hepatic metabolism17-19

*Bisoprolol must be used with caution in patients with: Diabetes mellitus showing large fluctuations in blood glucose values. Symptoms of hypoglycemia can be masked. **Although cardioselective (beta1) beta-blockers may have less effect on lung function than nonselective beta-blockers, as with all beta-blockers, these should be avoided in patients with obstructive airways diseases, unless there are compelling clinical reasons for their use. Bisoprolol is contra-indicated in patients with severe bronchial asthma.20 1. Neutel JM, et al. Am J Med. 1993 Feb;94(2):181-7. 2. Hiltunen TP, et al. Am J Hypertens. 2007 Mar;20(3):311-8. 3. Yang T, et al. Hypertens Res. 2017 Jan;40(1):79-86. 4. Stoschitzky K et al., Cardiology 2006;106:199-206. 5. von Arnim Th, et al. J Am Coll Cardiol. 1995;25:231–8. 6. CIBIS II Investigators and Committees. Lancet 1999;353:913. 7. Smith C, et al. Cardiovasc Drugs Ther. 1999;13(2):123-126. 8. Cruickshank JM. Shelton, CT: People's Medical Publishing House-USA;2011. Doc ID. 9. Janka HU, et al. J Cardiovasc Pharmacol. 1986;8(Suppl 11):S96–9. 10. Giesecke HG. and Bushner-Moil D. J Cardiovasc Pharmacol 1990;16(Suppl 5): S175-8. 11. Dorow P et al. Eur J Clin Pharmacol (1986) 31: 143-7. 12. Chang PC, et al. J Cardiovasc Pharmacol. 1988;12:317-22.13. Chang PC, et al. J Cardiovasc Pharmacol. 1986;8(Suppl 11):S58-60. 14. Bailliart O, et al. Eur Heart J. 1987;8(Suppl M):87-93. 15. Asmar RG, et al. Am J Cardiol. 1991;68(1):61-4. 16. Prisant LM, et al. J Clin Hypertens (Greenwich). 1999;1(1):22-6. 17. Leopold G. J Cardiovasc Pharmacol. 1986;8(Suppl 11):16-20. 18. Leopold G, et al. Rev Contemp Pharmacother. 1997;8:35-43. 19. Leopold G, et al. J Clin Pharmacol. 1986;26:616-21. 20. Concor®/Concor® COR. Product information (abbreviated prescribing information shortened for visual).